Retroviral vectors carrying various target regions of the HIV-1 genome (gag, pol, tat, rev, vif, and nef) are being constructed using strong viral (CMV), and cellular (Beta-actin and t-RNA) promoters to express the viral sequences. These sequences are in the antisense orientation relative to normal viral transcripts. These constructs will be stably integrated into H9 and U937 cells to evaluate the antiviral effects of high-level expression of particular antisense sequences. Those sequences have high antiviral activity will be further evaluated in HIV infection of primary human cells. In addition, promising antisense sequences will be dissected to identify the smallest possible regions having antiviral activity.